A variety of approaches have been used to alleviate symptoms in POTS (Postural Tachycardia Syndrome). Drugs reported to be of benefit include midodrine, propranolol, clonidine, and phenobarbital. Other measures used include volume expansion and physical countermaneuvers. These treatments may influence pathophysiologic mechanisms of POTS, such as alpha-receptor dysfunction, beta-receptor supersensitivity, venous pooling or brainstem center dysfunction. Little is know about effects of these interventions on hemodynamic indices in POTS, or whether changes in indices correlated with improvements in symptoms. The aim is to study hemodynamic indices and symptom scores in POTS patients acutely treated with a variety of interventions. We studied 22 subjects meeting the criteria of POTS [20 females, 1 male, ages 28.7 + 6.8 yrs, range 14-39]. Subjects were studied with a routine 5 minute tilt protocol, monitoring ECG, noninvasive beat-to-beat blood pressure and impedance plethysmography, before and after the administration of an intervention (i.v. saline, midodrine, propranolol, clonidine, or phenobarbital). The hemodynamic indices used were: heart period (ECG), systolic, mean, and diastolic blood pressure (Finapres), cardiac output, stroke volume, end-diastolic volume, and peak flow (impedance plethysmography), and total peripheral resistance (calculated). Subjects used a visual analog scale to record any change in their symptoms between the tilts. Symptoms scores improved significantly after midodrine and saline. Midodrine and propranolol reduced the resting heart rate (p < 0.005) and the immediate and 5 minute heart rate responses to tild (p < 0.002). Clonidine accentuated the immediate drop in blood pressure tilt-up (p < 0.05). Effects on other hemodynamic indices were complex. We conclude that midodrine and i.v. saline are effective in decreasing symptoms on tilt in patients with POTS when given acutely. Effects of treatments on heart rate and blood pressure responses generally reflected the known pharmacologic mechanisms of the agents. More complex effects on other hemodynamic indices will be discussed.